Pharmacokinetics Flashcards
Recall the 7 major routes by which drugs can be administered
- IV
- Intraperitoneal
- Oral
- Intramuscular
- Dermal
- Subcutaneous
- Inhalation
Recall an advantage and disadvantage of intraperitoneal administration
Advantage: richly perfused area
Disadvantage: requires training
Recall an advantage and disadvantage of drug inhalation
Advantage: well perfused region
Disadvantage: Danger with powder
Recall an advantage of dermal administration of a drug
Slow, sustained release
Recall an advantage and disadvantage of IV administration of a drug
Advantage: very rapid onset
Disadvantage: requires training
Recall 4 methods by which a drug might pass through a lipid bilayer
- Diffusion (if non-polar)
- Diffuse across aqueous pore (if polar)
- Carrier molecule
- Pinocytosis
Why do drugs often exist in both ionised and non-ionised forms?
Non-ionised form will easily cross lipid bilayer, ionised form will travel around body more easily
What affects the ratio of ionised: non-ionised drug?
pH
What is the pKa of aspirin?
3.4
Where does the majority of aspirin absorption take place and why?
Stomach - more of the unionised form here (driven by low pH) and so diffuses across lipid bilayer more easily
What is “ion trapping”?
Drug gets stuck in ionised form in aqueous compartment (?)
Recall the 4 factors affecting drug distribution
- Regional blood flow
- Extracellular binding to plasma proteins
- Capillary permeability
- Tissue localisation
How does protein-binding affect drug distribution?
Protein-bound drug no longer available for absorption
What sort of drugs are most likely to sjow tissue localisation?
Lipophillic drugs - accumulate in fatty tissue such as testes and brain
What are the 2 major routes of excretion of drugs?
Liver and Kidney
What sort of drugs tend to be excreted via the liver?
Drugs with a high MR that are lipophilic (dissolved in bile)
How may lipophobic drugs enter the bile
Active transport mechanisms - eg glucuronides
What problem may be caused by biliary excretion?
Enterohepatic cycling
How do drugs enter the urine once they have reached the kidney?
Active secretion (NOT ultrafiltration as large protein-bound complexes cannot be filtered)
What compound is used to increase aspirin secretion?
IV NaHCO3
Explain why IV sodium bicarbonate increases aspirin secretion
- NaHCO3 increases urine pH
- Aspirin is ionised –> less lipid soluble
- Less aspirin reabsorbed
What is “first pass metabolism”?
The concentration of a drug is greatly reduced before it reaches the systemic circulation, first passing through the hepatic circulation.
Define “enterohepatic circulation”
Drug/ metabolite excreted into gut (via bile) then reabsorbed, taken to liver and excreted again
What is first-order kinetics?
When the half life of a drug is constant
What is zero-order kinetics?
Drug is being eliminated at a constant rate
Define “bioavailability”
Proportion of administered drug available within body to exert pharmacological effect
Upon which 2 factors does drug clearance depend?
- Volume of distribution
2. Rate of drug elimination
Recall the equation used to calculate clearance for drugs that are cleared by first order kinetics
Volume of distribution = Kel (log2/ half life)
Recall the equation used to calculate clearance for drugs that are cleared by zero order kinetics
Time x Kel (change in conc/ change in time)
What is drug clearance?
Sum of metabolism by both liver and kidneys
